Skip to main content
SpringerLink
Log in

Effect of Forced Treadmill Running on Skeletal Muscle Myokine Levels in Mice with a Model of Type II Diabetes Mellitus

  • Experimental Papers
  • Published:
Journal of Evolutionary Biochemistry and Physiology Aims and scope Submit manuscript

Abstract

The effect of forced treadmill running on the level of some cytokines in skeletal muscles of mice with a model of type II diabetes mellitus was studied. The mouse model was developed using a 12-week high-fat diet; physical loading in the form of forced treadmill running was applied for 4 weeks. The concentration of myokines in m. gastrocnemius was determined by an enzyme-linked immunosorbent assay (ELISA). Diabetes formation in mice was accompanied by changes in the skeletal muscle concentration of two pro-inflammatory cytokines: an increase in IL-6 and a decrease in IL-15. Forced treadmill running loads had differential effects on the level of myokines in healthy and sick mice. In healthy animals, there was a decrease in IL-6 and IL-15 concentrations and an increase in the leukemia inhibitory factor (LIF) concentration in skeletal muscles after 4 weeks of regular forced running. At the same time, in diabetic mice, IL-6 and IL-15 concentrations increased, while the LIF concentration decreased after forced running loads. The NAP3 concentration in skeletal muscles was found to be insensitive to both the development of type II diabetes mellitus and regular forced treadmill running.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.
Fig. 2.
Fig. 3.
Fig. 4.

Similar content being viewed by others

REFERENCES

  1. Frontera WR, Ochala J (2015) Skeletal muscle: a brief review of structure and function. Calcif Tissue Int 96:183–195. https://doi.org/10.1007/s00223-014-9915-y

    Article  CAS  PubMed  Google Scholar 

  2. Sprenger H, Jacobs C, Nain M, Gressner A, Prinz H, Wesemann W, Gemsa D (1992) Enhanced release of cytokines, interleukin-2 receptors, and neopterin after long-distance running. Clin Immun Immunopathol 63:188–195. https://doi.org/10.1016/0090-1229(92)90012-d

    Article  CAS  Google Scholar 

  3. Drenth JP, Van Uum SH, van Deuren MG, Pesman J, Van der Ven-Jongekrijg J, Van der Meer JW (1995) Endurance run increases circulation IL-6 and IL-1ra but downregulatesex vivo TNF-α and Il-1α production. J Appl Physiol 79:1497–1503. https://doi.org/10.1152/jappl.1995.79.5.1497

    Article  CAS  PubMed  Google Scholar 

  4. Nehlsen-Cannarella SL, Fagoaga OR, Nieman DC, Henson DA, Butterworth DE, Schmitt RL, Bailey EM, Warren BJ, Utter A, Davis JM (1997) Carbohydrate and the cytokine response to 2.5 h of running. J Appl Physiol. 82:1662–1667. https://doi.org/10.1152/jappl.1997.82.5.1662

    Article  CAS  PubMed  Google Scholar 

  5. Ostrowski K, Ronde T, Asp S, Schjerling P, Pedersen BK (1999) Pro- and anti-inflammatory cytokine balance in strenuous exercise in humans. J Physiol 515:287–291. https://doi.org/10.1111/j.1469-7793.1999.287ad.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Steensberg A, van Hall G, Osada T, Sacchetti M, Saltin B, Pedersen B (2000) Production of interleukin-6 in contracting human skeletal muscles can account for the exercise-induced increase in plasma interleukin-6. J Physiol 529:237–242. https://doi.org/10.1111/j.1469-7793.2000.00237.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Keller C, Steensberg A, Pilegaard H, Osada T, Saltin B, Pedersen BK, Neufer PD (2001) Transcriptional activation of the IL-6 gene in human contracting skeletal muscle: influence of muscle glycogen content. FASEB J 15:2748–2750. https://doi.org/10.1096/fj.01-0507fje

    Article  CAS  PubMed  Google Scholar 

  8. Kapilevich LV, Kabachkova AV, Zakharova AN, Lalaeva GS, Kironenko TA, Dyakova EYu, Orlov SN (2016) Secretory Function of Skeletal Muscles: Producing Mechanisms and Myokines Physiological Effects. Uspekhi Fiziol Nauk 47(2):7–26. (In Russ). PMID: 27530041

  9. Pedersen BK, Febbraio MA (2008) Muscle as an endocrine organ: focus on muscle-derived interleukin-6. Physiol Rev 88:1379–1406. https://doi.org/10.1152/physrev.90100.2007

    Article  CAS  PubMed  Google Scholar 

  10. Iizuka K, Machida T, Hirafuji M (2014) Skeletal muscle is an endocrine organ. J Pharmacol Sci 125:125–131. https://doi.org/10.1254/jphs.14r02cp

    Article  CAS  PubMed  Google Scholar 

  11. Pedersen BK, Febbraio MA (2012) Muscles, exercise and obesity: skeletal muscle as a secetory organ. Nat Rev Endocrinol 8:457–465. https://doi.org/10.1038/nrendo.2012.49

    Article  CAS  PubMed  Google Scholar 

  12. Groop LC, Eriksson JG (1992) The etiology and pathogenesis of non-insulin-dependent diabetes. Ann Med 24(6):483–489. https://doi.org/10.1002/dmr.5610090503

    Article  CAS  PubMed  Google Scholar 

  13. Fujimaki S, Kuwabara T (2017) Diabetes-induced dysfunction of mitochondria and stem cells in skeletal muscle and the nervous system. Int J Mol Sci 18(10):2147. https://doi.org/10.3390/ijms18102147

    Article  CAS  PubMed Central  Google Scholar 

  14. Højlund K (2014) Metabolism and insulin signaling in common metabolic disorders and inherited insulin resistance. Dan Med J 61(7):B4890. PMID: 25123125

  15. Nagy C, Einwallner E (2018) Study of In vivo glucose metabolism in high-fat diet-fed mice using oral glucose tolerance test (OGTT) and insulin tolerance test (ITT). J Vis Exp 7(131):1–12. https://doi.org/10.3791/56672

    Article  CAS  Google Scholar 

  16. Huh JY (2018) The role of exercise-induced myokines in regulating metabolism. Arch Pharm Res 41(1):14–29. https://doi.org/10.1007/s12272-017-0994-y

    Article  CAS  PubMed  Google Scholar 

  17. Meneilly GS (2001) Pathophysiology of diabetes in the elderly. In: Diabetes in old age. John Wiley & Sons 155–164. https://doi.org/10.1002/0470842326.ch2

    Chapter  Google Scholar 

  18. Brandt C, Pedersen BK (2010) The role of exercise-induced myokines in muscle homeostasis and the defense against chronic diseases. J Biomed Biotechnol 2010:520258. https://doi.org/10.1155/2010/520258

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Hansen JS, Zhao X, Irmler M, Liu X, Hoene M, Scheler M, Li Y, Beckers J, Hrabĕ de Angelis M, Häring HU, Pedersen BK, Lehmann R, Xu G, Plomgaard P, Weigert C (2015) Type 2 diabetes alters metabolic and transcriptional signatures of glucose and amino acid metabolism during exercise and recovery. Diabetologia 58:1845–1854. https://doi.org/10.1007/s00125-015-3584-x

    Article  CAS  PubMed  Google Scholar 

  20. Karstoft K, Pedersen BK (2016) Exercise and type 2 diabetes: focus on metabolism and inflammation. Immunol Cell Biol 94:146–150. https://doi.org/10.1038/icb.2015.101

    Article  CAS  PubMed  Google Scholar 

  21. Kapilevich L, Zakharova A, Kabachkova A, Kironenko T, Milovanova K, Orlov S (2017) Different impact of physical activity on plasma myokines content in athletes and untrained volunteers. FEBS J 284(1):373–373. WOS:000409918904202

  22. Kapilevich LV, Zakharova AN, Kabachkova AV, Kironenko TA, Orlov SN (2017) Dynamic and static exercises differentially affect plasma cytokine content in elite endurance- and strength-trained athletes and untrained volunteers. Front Physiol 8:35. https://doi.org/10.3389/fphys.2017.00035

    Article  PubMed  PubMed Central  Google Scholar 

  23. Winzell MS, Ahren B (2004) The high-fat diet-fed mouse: a model for studying mechanisms and treatment of impaired glucose tolerance and type 2 diabetes. Diabetes 53(3):S215–S219. https://doi.org/10.2337/diabetes.53.suppl_3.s215

    Article  PubMed  Google Scholar 

  24. Kapilevich LV, Zakharova AN, Dyakova EYu, Kalinnikova JG, Chibalin AV (2019) Mice experimental model of diabetes mellitus type ii based on high fat diet. Bull Siberian Med 18(3):53–61. https://doi.org/10.20538/1682-0363-2019-3-53-61

    Article  Google Scholar 

  25. Zakharova AN, Kalinnikova Y, Negodenko ES, Orlova AA, Kapilevich LV (2020) Experimental simulation of cyclic training loads. Teor Prakt Fizich Kult 10:26–27.

  26. Schwartz V (2009) Regulation of metabolic processes by interleukin-6. Cytokines and Inflam 3:3–10. (In Russ).

  27. Pedersen BK, Steensberg A, Fischer C, Keller C, Keller P, Plomgaard P, Febbraio M, Saltin B (2003) Searching for the exercise factor:: is IL-6 a candidate? J Muscle Res Cell Motil 24(2-3):113–119. https://doi.org/10.1023/a:1026070911202

    Article  CAS  PubMed  Google Scholar 

  28. Pedersen BK, Fischer CP (2007) Beneficial health effects of exercise: the role of Il-6 as a myokine. Trends Pharmacol Sci 28:152–156. https://doi.org/10.1016/j.tips.2007.02.002

    Article  CAS  PubMed  Google Scholar 

  29. Malashenkova IK, Casanova GV, Didkovsky NA (2014) Interleukin-15: structure, signaling and role in immune defense. Molec Med 3:9–20. (In Russ).

  30. Quinn LS, Strait-Bodey L, Anderson BG, Argilés JM, Havel PJ (2005) Interleukin-15 stimulates adiponectin secretion by 3T3-L1 adipocytes: evidence for a skeletal muscle-to-fat signaling pathway. Cell Biol Int 29:449–457. https://doi.org/10.1016/j.cellbi.2005.02.005

    Article  CAS  PubMed  Google Scholar 

  31. Broholm C, Pedersen BK (2010) Leukemia inhibitory factor – an exercise-induced myokine. Exerc Immunol Rev 16:77–85. PMID:20839492

  32. Srikuea R, Esser KA, Pholpramool C (2011) Lekemia factor is expressed in rat gastrocnemius muscle after contusion and increases proliferation of rat L6 myoblasts via c-Myc signalling. Clin Exp Pharmacol Physiol 38:501–509. https://doi.org/10.1111/j.1440-1681.2011.05537.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Pedersen BK, Saltin B (2015) Exercise as medicine – evodence for prescribing exercise as therapy in 26 different chronic diseases. Scand J Med Sci Sports 25:1–72. https://doi.org/10.1111/sms.12581

    Article  PubMed  Google Scholar 

  34. Pedersen L, Pilegaard H, Hansen J, Brandt C, Adser H, Hidalgo J, Olesen J, Pedersen BK, Hojman P (2011) Exercise-induced liver chemokine CXCL-1 expression is linked to muscle-derived interleukin-6 expression J Physiol 589(6):1409–1420. https://doi.org/10.1113/jphysiol.2010.200733

  35. Pedersen L, Olsen CH, Pedersen BK, Hojman P (2012) Muscle-derived expression of the chemokine CXCL1 attenuates diet-induced obesity and improves fatty acid oxidation in the muscle. Am J Physiol Endocrinol Metab 302(7):831–840. https://doi.org/10.1152/ajpendo.00339.2011

    Article  CAS  Google Scholar 

  36. Peake JM, Gatta PD, Suzuki K, Nieman DC (2015) Cytokine expression and secretion by skeletal muscle cells: regulatory mechanisms and exercise effects. Exercise Immunol Rev 21:8–25. PMID: 25826432

  37. Fitts RH, Widrick JJ (1996) Muscle mechanics: adaptations with exercise-training. Exerc Sport Sci Rev 24:427–473. PMID: 8744258

  38. Raue U, Trappe T.A, Estrem S.T, Qian H-R, Helvering LM, Smith RC, Trappe S (2012) Transcriptomic signature of resistance exercise adaptations: mixed muscle and fiber type specific profiles in young and old adults. J Appl Physiol 112:1625–1636. https://doi.org/10.1152/japplphysiol.00435.2011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Gundersen K (2011) Excitation-transcription coupling in skeletal muscle: the molecular pathways of exercise. Biol Rev 86:564–600. https://doi.org/10.1111/j.1469-185X.2010.00161.x

    Article  PubMed  Google Scholar 

  40. Kapilevich LV, Kironenko TA, Zaharova AN, Kotelevtsev YV, Dulin NO, Orlov SN (2015) Skeletal muscle as an endicrine organ: role of [Na+]i/[K+]i-mediated excitation-transcription coupling. Gen Diseas 2:328–336. https://doi.org/10.1016/j.gendis.2015.10.001

    Article  Google Scholar 

  41. Ma H, Groth RD, Wheeler DG, Barrett CF, Tsien RW (2011) Excitation-transcription coupling in sympathetic neurons and the molecular mechanism of its initiation. Neurosci Res 70:2–8. https://doi.org/10.1016/j.neures.2011.02.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Holmes AG, Watt MJ, Carey AL, Febbraio MA (2004) Ionomycin, but not physiological doses of epinephrine, stimulates skeletal muscle interleukin-6 mRNA expression and protein release. Metabolism 53:1492–1495. https://doi.org/10.1016/j.metabol.2004.05.015

    Article  CAS  PubMed  Google Scholar 

  43. Whitham M, Chan MHS, Pal M, Matthews VB, Prelovsek O, Lunke S, El-Osta A, Broenneke H, Alber J, Brüning JC, Wunderlich FT, Lancaster GI, Febbraio MA (2012) Contraction-induced interleukin-6 gene transcription in skeletal muscle is regulated by c-Jun terminal kinase/activator protein-1. J Biol Chem 287:10771–10779. https://doi.org/10.1074/jbc.M111.31058

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Nedachi T, Hatakeyama H, Kono T, Sato M, Kanzaki M (2009) Charactrization of contraction-inducible CXC chemokines and their roles in C2C12 myocytes. Am J Physiol Endocrinol Metab 297:E866–E878. https://doi.org/10.1152/ajpendo.00104.2009

    Article  CAS  PubMed  Google Scholar 

  45. McKenna MJ, Bangsbo J, Renaud JM (2008) Muscle K+, Na+, and Cl– disturbances and Na+-K+ pump inactivation: implications for fatigue. J Appl Physiol 104:288–295. https://doi.org/10.1152/japplphysiol.01037.2007

    Article  CAS  PubMed  Google Scholar 

  46. Koltsova SV, Trushina Y, Haloui M, Akimova OA, Tremblay J, Hamet P, Orlov SN (2012) Ubiquitous [Na+]i/[K+]i-sensitive transcriptome in mammalian cells: evidence for [Ca2+]i-independent excitation-transcription coupling. PLoS One 7:e38032. https://doi.org/10.1371/journal.pone.0038032

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This work was supported by the Russian Science Foundation, grant No. 19-15-00118.

Author information

Authors and Affiliations

  1. National Research Tomsk State University, Tomsk, Russia

    A. N. Zakharova, T. A. Kironenko, K. G. Milovanova, A. A. Orlova, E. Yu. Dyakova, Yu. G. Kalinnikova, A. V. Chibalin & L. V. Kapilevich

  2. Siberian State Medical University, Tomsk, Russia

    L. V. Kapilevich

  3. Department of Molecular Medicine and Surgery, Integrative Physiology, Karolinska Institute, Stockholm, Sweden

    A. V. Chibalin

Authors
  1. A. N. Zakharova
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T. A. Kironenko
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. K. G. Milovanova
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A. A. Orlova
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. E. Yu. Dyakova
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yu. G. Kalinnikova
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. A. V. Chibalin
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. L. V. Kapilevich
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

A.N.Z., E.Yu.D., A.V.C., and L.V.K. contributed to the development of the concept and methodology of this study, data analysis, writing and editing the manuscript; T.A.K., K.G.M., A.A.O., and Yu.G.K. directly participated in experimental studies.

Corresponding author

Correspondence to L. V. Kapilevich.

Ethics declarations

CONFLICT OF INTEREST

The authors declare that this study has been performed without any commercial or financial relationships that might be interpreted as a potential conflict of interest.

Additional information

Translated by A. Polyanovsky

Russian Text © The Author(s), 2021, published in Rossiiskii Fiziologicheskii Zhurnal imeni I.M. Sechenova, 2021, Vol. 107, Nos. 6–7, pp. 864–875https://doi.org/10.31857/S0869813921060157.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zakharova, A.N., Kironenko, T.A., Milovanova, K.G. et al. Effect of Forced Treadmill Running on Skeletal Muscle Myokine Levels in Mice with a Model of Type II Diabetes Mellitus. J Evol Biochem Phys 57, 904–912 (2021). https://doi.org/10.1134/S0022093021040141

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0022093021040141

Keywords:

Search

Navigation